1. Field of the Invention
The present invention relates generally to the field of medical apparatus and instrumentation and more particularly to the field of non-pharmacologic treatment of cardiac disorders including arrhythmias and ischemias, including percutaneous treatment, with specific application to the ablation or modification of tissues responsible for the arrhythmia, and for protection of ischemia reperfusion injury by application of local hyperthermal treatment.
2. Description of the Related Art
Cardiac arrhythmias arise when the rhythmic electrical signal from the heart's intrinsic pacemakers is not correctly propagated throughout the heart. A particular type of cardiac arrhythmia is a ventricular tachycardia, in which an ectopic focus occurs in the ventricle of the heart resulting in a heartbeat of over 100 beats per minute. This problem often occurs near a site of damaged myocardial tissue caused by an infarction or other injury.
Heating and thus coagulating ("ablating") myocardial tissues responsible for cardiac arrhythmias has been shown to be of great therapeutic value and is frequently done percutaneously ("catheter ablation"). By far the most common method involves delivering radiofrequency energy (RF) via a catheter with a flexible tip equipped with electrodes for sensing ("mapping") the endocardial electrical activation sequence, and for delivering RF energy or laser energy (see Svenson et al., U.S. Pat. No. 5,172,699). The arrhythmias which respond best to this therapy (with a &gt;90% cure rate) are supraventricular. This is due (1) to well-defined mapping criteria highly predictive of cure and (2) to the small volume of tissue which, when ablated, prevents recurrent arrhythmia. Thus only few, or sometimes one, relatively superficial but well targeted, RF-induced lesion(s) may be necessary for success.
This same approach has been far less successful in treating the ventricular arrhythmias typically originating from tissues damaged by myocardial infarction. RF catheter ablation can be recommended only as adjunctive (not "first line") therapy for these arrhythmias. Reasons for this, again, are (1) mapping criteria which are not as clearly correlated with success as in the case of supraventricular arrhythmias and (2) larger tissue volume responsible for the arrhythmia.
An attempt to address the problem of ventricular arrhythmias is described by Isner and Clarke, U.S. Pat. No. 5,104,393, which discloses a catheter for ablation of cardiac tissue. The instrument tip is held in place in the endocardium by a fixation wire, with the ablation tip held on the endocardial wall, and thus, the tip does not directly reach deep intramyocardial tissue where arrhythmias may arise. Other present methods are similarly inadequate for ablating such deep tissue, precluding percutaneous treatment for many patients.
In recent years there has been significant interest in generating elevated levels of heat shock proteins (HSP's) in the heart and examining their cardioprotective abilities. These efforts have led to the development of experimental protocols in which different stresses such as hypoxia, mechanical strain, hemodynamic overload and hypothermia have been used to express HSP's (especially the HSP70 family) and examine the subsequent protection to the heart from ischemia/reperfusion (I/R) injury.
Previous work in various in-vitro and in vivo animal models has shown that hyperthermia-induced expression of HSP's is accompanied by protection against ischemia/reperfusion (I/R) injury of the heart (Marber et al. 1993; Donnely et al. 1992; Yellon et al. 1992; Walker et al. 1993; Currie et al. 1993). This protection has not only been shown to be related to HSP expression but also directly correlated to the amount of HSP induced before I/R (Hutter et al. 1994). Additionally, expression of HSP's as a result of heat shock response has been shown to improve functional recovery after ischemia and reperfusion (Currie et al. 1988).
In previous hyperthermia studies HSP expression was achieved by either heating the buffer solutions of in vitro isolated hearts or by subjecting animals to whole body hyperthermia 24 hours before I/R. However, whole body heat stress may exert negative effects on extracardiac cells such as blood cells, as the observed duration of cardioprotection in animals treated with whole body hyperthermia in vivo is less than cardioprotection of hearts heat shocked during isolated buffer perfusion in vitro. Walker et al. demonstrated these extracardiac effects in experiments in which buffer perfused hearts and blood (non-heat shock) perfused hearts of animals subjected to whole body hyperthermia were able to withstand longer periods of ischemia than animals subjected to whole body hyperthermia whose hearts were still perfused by the heat shocked blood components.
Their is a need therefore for a method of directly heating the heart and inducing regional HSP expression, thus avoiding limitations that may be induced during whole body hyperthermia.